Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study (TRAIN-3)
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|ClinicalTrials.gov Identifier: NCT03820063|
Recruitment Status : Active, not recruiting
First Posted : January 29, 2019
Last Update Posted : February 22, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: PTC-Pz||Phase 2|
High pathological complete response (pCR)-rates are seen using different neoadjuvant chemotherapy schedules with trastuzumab and pertuzumab in HER2-positive stage II - III breast cancer patients. Total pCR rates in breast and axilla have been described as high as 64%, and with an even higher rate of >80% in patients with HER2-positive and hormone receptor (HR) negative tumors. PCR is associated with better long-term outcomes in patients with HER2-positive breast cancer. Three year progression-free survival ranges between 85-90%. Neoadjuvant treatment of HER2-positive breast cancer typically consists of six to nine cycles of treatment. Longer duration of treatment is associated with higher pCR-rates but gives more toxicity. Pathological complete responses are sometimes seen after only 10-12 days of neoadjuvant treatment. It is therefore important to investigate which patients can safely be treated with less than six cycles of chemotherapy and who requires more than six cycles for maximum activity.
The radiologic response of a breast tumor after neoadjuvant therapy is predictive of the pathologic response, although the accuracy differs between breast cancer subtypes. It is hypothesized that patients with an early complete radiologic response may not benefit from additional chemotherapy and can be referred for early surgery. Patients who have not achieved pCR after early surgery despite radiologic complete response (rCR) are candidates for further adjuvant chemotherapy to complete the initially planned number of treatment cycles and maintain maximum treatment activity. Imaged guided de-escalation in which the number of treatment cycles is determined by the radiologic response could thus reduce toxicity in neoadjuvant treatment while maintaining activity.
This study will evaluate the efficacy of image-guided de-escalation of neoadjuvant chemotherapy in patients with HER2-positive breast cancer.
To maintain efficacy, patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1. Patients who achieve early pCR will continue treatment with Herceptin® and pertuzumab to complete one full year of treatment.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||462 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||neoadjuvant courses PTC-Ptz; adjuvant courses Ptz (pCR) or T-DM1 (non-pCR)|
|Masking:||None (Open Label)|
|Official Title:||Image-guided De-escalation of Neo-adjuvant Chemotherapy in HER2-positive Breast Cancer: the TRAIN-3 Study|
|Actual Study Start Date :||February 27, 2019|
|Actual Primary Completion Date :||November 15, 2022|
|Estimated Study Completion Date :||May 1, 2032|
Patients who do not achieve pCR will complete a total of nine cycles taxane-containing chemotherapy followed by 14 cycles of treatment with adjuvant T-DM1.
In case of non pCR; Adjuvant T-DM1, 3.6mg/kg Q 22 days, for 14 cycles.
- Event free survival at three years [ Time Frame: 3 years ]Number of patients without progression of disease recurrence, second primary or death
- Overall survival at three years [ Time Frame: 3 years ]Number of patients alive at three years
- Pathologic complete response in breast and axilla [ Time Frame: an average of 6 months ]Number of patients with absence of invasive tumor cells in breast and axilla at surgery
- Radiologic complete response [ Time Frame: an average of 6 months ]Number of patients with absence of pathologic enhancement on MRI
- Number of neoadjuvant chemotherapy cycles administered [ Time Frame: an average of 1 year ]Number of neoadjuvant chemotherapy cycles administered per patient
- Number of radical and non-radical resections [ Time Frame: an average of 6 months ]Number of patients with radical and non-radical resections
- Incidence and severity of adverse events [ Time Frame: an average of 1 year ]Number of patients with toxicity grade >= 3 (CTCAE v5.0) until 30 days after last adjuvant administration
- Incidence and severity of cardiotoxicity and neuropathy [ Time Frame: an average of 1 year ]Number of patients with cardiotoxicity and neuropathy grade >= 2 (CTCAE v5.0) until 30 days after last adjuvant administration
- Incidence of symptomatic LVSD (heart failure), [ Time Frame: an average of 1 year ]Number of patients with an asymptomatic decline in LVEF requiring treatment or leading to discontinuation of pertuzumab and Herceptin, or a decrease ≥10 percentage points from baseline to a LVEF <50%
- Grade ≥3 laboratory test abnormalities [ Time Frame: an average of 1 year ]Number of patients with Grade ≥3 laboratory test abnormalities
- Incidence of number of tumor positive Vacuum Assisted Core Biopsy [ Time Frame: an average 6 months ]Number of patients with tumor present at Vacuum Assisted Core Biopsy at the moment of radiological complete response on MRI
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Histologically confirmed primairy infiltrating breast cancer.
- Stage II or Ill disease.
- Overexpression and/or amplification of HER2 in an invasive component of the core biopsy.
- Age <:18
- ECOG Group performance status
- LVEF >50% measured by echocardiography, MRI or MUGA
- Known HR-status ( in percentages)
- Previous radiation therapy of chemotherapy
- Pregnancy or breastfeeding
- Evidence of distant metastases
- Evidence of bilateral infiltrating breast cancer
- Concurrent anti-cancer treatment or another investigational drug
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03820063
|Principal Investigator:||G S Sonke, MD||NKI-AvL|
|Study Director:||A E van Leeuwen- Stok, PhD||BOOG Study Center|
|Responsible Party:||Borstkanker Onderzoek Groep|
|Other Study ID Numbers:||
|First Posted:||January 29, 2019 Key Record Dates|
|Last Update Posted:||February 22, 2023|
|Last Verified:||February 2023|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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